Physiological Umbilical Cord Clamping in Patients With Congenital Diaphragmatic Hernia. Clinical Trial
- Conditions
- Umbilical Cord ClampingDelayed Umbilical Cord SeparationCongenital Diaphragmatic Hernia
- Interventions
- Procedure: Physiological cord clamping
- Registration Number
- NCT06408376
- Lead Sponsor
- Hospital JP Garrahan
- Brief Summary
Congenital diaphragmatic hernia (CDH) is a malformation that affects 1 in every 3000 newborns. The diaphragm does not complete its closure during embryogenesis, which allows the abdominal organs to herniate into the thoracic cavity altering lung development. The lungs of patients with CDH are small, with a decreased surface area for gas exchange and developmental impair of the pulmonary vasculature, resulting in respiratory failure and pulmonary hypertension shortly after birth. When clamping the umbilical cord, a large part of the preload is abruptly excluded, generating an increase in vascular resistance, which in turn increase the afterload, resulting in a decrease in cardiac output. The output is restored by decreasing vascular resistance in pulmonary circuit after lung aeration upon receiving the preload of the right atrium, increasing pulmonary flow and thus sustaining the preload of the left ventricle. If pulmonary aeration occurs before clamping the umbilical cord, the pulmonary blood flow increases before placenta flow is lost, thus avoiding a decrease in cardiac output. This modality has been called physiological base cord clamping (PFC). The hypothesis is that PFC once ventilation has been established could prevent hypoxia and improve cardiac output in newborns with CDH and secondarily improve their hemodynamic parameters, stabilizing gas exchange and pulmonary hypertension during the first 24 hours of birth.
- Detailed Description
* Type of study: Randomized clinical trial
* Primary objective: To establish the effectiveness of PFC in reducing hypoxia and improving cardiac output compared to immediate postintubation clamping in newborns with CDH. To establish the safety and feasibility of PFC after pulmonary recruitment achieved post intubation.
* Secondary objectives: describe the evolution of patients with CDH 24 hours after birth under pre-established conditions. Relate prenatal indices to the subsequent evolution of these patients. Describe maternal evolution and postpartum complications.
* Population: Patients who attend the Fetal Diagnosis and Treatment program of Garrahan Children's Hospital and undergo prenatal diagnosis of CDH are possible candidates. The study will be carried out in the Neonatal Intensive Care Unit of said hospital.
* Scope of the study: Garrahan Children's Hospital is a level 3 B pediatric hospital and national referral center located in Autonomous City of Buenos Aires, Argentina. Center that receives neonates with CDH referred from all over the country as well as from other countries in the region and carries out the relevant training for equal reception.
* Block randomization: will be carried out on the same day, 2 hours before entering the delivery room
* Intervention: Immediately after birth, the newborn will be placed on a mobile table, made to received these patients in the delivery room, at the level of the mother's womb, leaving the umbilical cord intact, intubated and gently ventilated (positive inspiration pressure (PIM) 15/25 - positive end expiratory pressure (PEEP)4 - fraction of inspired oxygen inspired oxygen fraction (FiO2) 50%), until saturation \>85% and heart rate (HR) \>100 or 10 timed minutes pass, whichever occurs first, the umbilical cord will be clamped and continued with the usual reception steps in accordance with the unit´s CDH reception protocol.
* Sample size: To calculate the sample size, a prevalence of hemodynamic alterations of 60% was considered in the first 24 hours of life of patients with CDH, following unit statistics and the aforementioned bibliography. The estimated sample size with a relative reduction of 50%: reduction from 60% to 30% of hemodynamic alterations - Power of 80% - Two-tailed test - alpha 5%. 40 patients required in each branch.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
- Prenatal diagnosis of congenital diaphragmatic hernia
- gestational age >34 weeks
- Informed consent signed by the patient's parents
- Multiple gestation
- Major malformation or fetal genetic anomaly diagnosed in the prenatal stage
- Emergency cesarean section or maternal condition that prevents the approach
- Lack of informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description physiological umbilical cord clamping Physiological cord clamping Immediately after birth, the newborn will be placed on a mobile table, made to receive these patients in the delivery room, at the level of the mother's womb, leaving the umbilical cord intact and will be intubated. The patient will be gently ventilated (PIM 15/25 - PEEP 4 - Fio2 50%), until saturation \>85% and HR\>100 or 10 timed minutes have elapsed, whichever occurs first, the umbilical cord will be clamped and the procedures continued usual reception steps according to the unit´s CDH reception protocol.
- Primary Outcome Measures
Name Time Method complete delivery according group delivery Complete the protocol in the delivery room pre-established according to randomization (yes/no)
Hemodynamic deterioration in the first 24 hours of life 24 hours of life Hemodynamic deterioration in the first 24 hours of life (meeting 3 of 4 of the following criteria or entry to extracorporeal membrane oxygenation (ECMO) or Death).
1. Pre/post ductal saturation difference \>10%
2. Oxygenation index (IO) \>20
3. mean arterial pressure \< Percentile 50 or inotrope requirement
4. Lactic acid \>3 mmol/l
- Secondary Outcome Measures
Name Time Method Intubation time From delivery to intubation Time to intubation (minutes, seconds)
Gestational age at diagnosis 1st day of life Gestational age at diagnosis of CDH in weeks
Cord clamping time from delivery to cord clamping Cord clamping time (minutes, seconds)
Time to reach heart rate (HR) >100 from delivery to 30 minutes of life Time to reach HR \>100 (minutes, seconds)
Mother arterial tension after delivery 10 minutes after delivery mothers arterial mean tension after delivery in mmhg
Oxygenation on the first day 2 - 4 hours and 24 hours of life Partial arterial pressure of oxygen (PaO2) mmhg
PH value on the first day 6 and 24 hours of life echocardiographic pulmonary hypertension PH (\<50% of systemic pressure, between 50-80% of systemic pressure, between 80 and 100% of systemic pressure, systemic, suprasystemic)
lung volumen from 26 to 32 weeks of gestational age lung volumen in RMI
liver in thorax from 26 to 32 weeks of gestational age liver in thorax (yes/no) and %
Cord lactic acid value inmediatly after cord clampping cord lactic acid value in mmol/l
near-infrared spectroscopy (Nirs) on the first day 2 - 4 hours and 24 hours of life Cerebral and somatic NIRS
cardiac malformations 6 hours of life cardiac malformation (yes/no)
Mcgoon from 26 to 32 weeks of gestational age Mcgoon Index in fetal echocardiogram
Advance resuscitation need on delivery room from delivery to 30 minutes of life Requirement for advanced resuscitation (yes/no) (compressions, drugs, hypothermia)
Arterial pressure at 10 minutes 10 minutes of life mean arterial tension in mmhg
Uterotonic use 30 minutes after delivery uterotonics use on mothers after delivery (yes/no)
Evolution of patient inotropes required 2 - 4 hours and 24 hours of life Inotrope requirement (yes/no)
ventilation requirements on the first day 2 - 4 hours and 24 hours of life Ventilatory mode / mean airway pressure (MAP)/ FIo2 %
Oxygenation index (OI) on the first day 2 - 4 hours and 24 hours of life OI
B natriuretic peptide (BNP) on the first day 24 hours of life B natriuretic peptide (BNP)
Admission to ECMO through study completion, an average of 1 year Admission to ECMO after the first 24 hours (yes/no)
Lung heart rate index observed/expected LHR O/E from 26 to 32 weeks of gestational age lung heart rate index observed/expected (LHR O/E)
stomach herniation from 26 to 32 weeks of gestational age stomach herniation (yes/no) and %
maternal hematocrit 1 day before delivery maternal hematocrit in gr/dl
Time to reach saturation (SAT) >85% from delivery to 30 minutes of life Time to reach SAT \>85% (minutes, seconds)
Evolution of patient Blood preassure (BP) 2 - 4 hours and 24 hours of life Blood pressure in mmhg
Mortality through study completion, an average of 1 year Mortality (yes/no)
Cord PH value inmediatly after cord clampping cord ph value
saturation at 10 minutes 10 minutes of life pre and post ductal saturation %
placenta abruption 30 minutes of life Time for placental abruption (minutes, seconds)
Inhaled nitric oxide (NOi) requirement 2 - 4 hours and 24 hours of life NOi requirement (yes/no)
Trial Locations
- Locations (1)
Hospital de Pediatría S.A.M.I.C. "Prof. Dr. Juan P. Garrahan"
🇦🇷Buenos Aires, Argentina